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Fibroblast activation protein

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https://www.readbyqxmd.com/read/29913199/genome-wide-profiling-of-adult-human-papillary-and-reticular-fibroblasts-identifies-acan-col-xi-%C3%AE-1-and-psg1-as-general-biomarkers-of-dermis-ageing-and-kank4-as-an-exemplary-effector-of-papillary-fibroblast-ageing-related-to-contractility
#1
Valérie Haydont, Véronique Neiveyans, Hélène Zucchi, Nicolas O Fortunel, Daniel Asselineau
Deciphering the characteristics of dermal fibroblasts is critical to further understand skin ageing. We have conducted a genome-wide transcriptomic characterization of papillary (Fp) and reticular (Fr) fibroblasts extracted from human skin samples corresponding to younger and older adult ages. From this screen, biomarkers suitable for the assessment of chronological ageing were identified, and extrapolated to the context of photo-damaged skin. In particular, KANK4, ACAN, Col XI α1, and PSG1, were expressed at an increased level in both chronologically-aged and photo-damaged skin...
June 15, 2018: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29912986/a-recombinant-herpesviral-vector-containing-a-near-full-length-sivmac239-genome-produces-siv-particles-and-elicits-immune-responses-to-all-nine-siv-gene-products
#2
Young C Shin, Georg F Bischof, William A Lauer, Lucas Gonzalez-Nieto, Eva G Rakasz, Gregory M Hendricks, David I Watkins, Mauricio A Martins, Ronald C Desrosiers
The properties of the human immunodeficiency virus (HIV) pose serious difficulties for the development of an effective prophylactic vaccine. Here we describe the construction and characterization of recombinant (r), replication-competent forms of rhesus monkey rhadinovirus (RRV), a gamma-2 herpesvirus, containing a near-full-length (nfl) genome of the simian immunodeficiency virus (SIV). A 306-nucleotide deletion in the pol gene rendered this nfl genome replication-incompetent as a consequence of deletion of the active site of the essential reverse transcriptase enzyme...
June 18, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29910813/s100a4-is-secreted-by-alternatively-activated-alveolar-macrophages-and-promotes-activation-of-lung-fibroblasts-in-pulmonary-fibrosis
#3
Wei Zhang, Shinji Ohno, Beatrix Steer, Stephan Klee, Claudia A Staab-Weijnitz, Darcy Wagner, Mareike Lehmann, Tobias Stoeger, Melanie Königshoff, Heiko Adler
Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease, characterized by damage of lung epithelial cells, excessive deposition of extracellular matrix in the lung interstitium, and enhanced activation and proliferation of fibroblasts. S100a4, also termed FSP-1 (fibroblast-specific protein-1), was previously considered as a marker of fibroblasts but recent findings in renal and liver fibrosis indicated that M2 macrophages are an important cellular source of S100a4. Thus, we hypothesized that also in pulmonary fibrosis, M2 macrophages produce and secrete S100a4, and that secreted S100a4 induces the proliferation and activation of fibroblasts...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29910803/expression-of-programmed-death-ligand-1-by-human-colonic-cd90-stromal-cells-differs-between-ulcerative-colitis-and-crohn-s-disease-and-determines-their-capacity-to-suppress-th1-cells
#4
Ellen J Beswick, Carl Grim, Abinav Singh, Jose E Aguirre, Marissa Tafoya, Suimin Qiu, Gerhard Rogler, Rohini McKee, Von Samedi, Thomas Y Ma, Victor E Reyes, Don W Powell, Irina V Pinchuk
Background and Aims: The role of programmed cell death protein 1 (PD-1) and its ligands in the dysregulation of T helper immune responses observed in the inflammatory bowel disease (IBD) is unclear. Recently, a novel concept emerged that CD90+ colonic (myo)fibroblasts (CMFs), also known as stromal cells, act as immunosuppressors, and are among the key regulators of acute and chronic inflammation. The objective of this study was to determine if the level of the PD-1 ligands is changed in the IBD inflamed colonic mucosa and to test the hypothesis that changes in IBD-CMF-mediated PD-1 ligand-linked immunosuppression is a mechanism promoting the dysregulation of Th1 cell responses...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29907658/degradation-of-dendritic-cargos-requires-rab7-dependent-transport-to-somatic-lysosomes
#5
Chan Choo Yap, Laura Digilio, Lloyd P McMahon, A Denise R Garcia, Bettina Winckler
Neurons are large and long lived, creating high needs for regulating protein turnover. Disturbances in proteostasis lead to aggregates and cellular stress. We characterized the behavior of the short-lived dendritic membrane proteins Nsg1 and Nsg2 to determine whether these proteins are degraded locally in dendrites or centrally in the soma. We discovered a spatial heterogeneity of endolysosomal compartments in dendrites. Early EEA1-positive and late Rab7-positive endosomes are found throughout dendrites, whereas the density of degradative LAMP1- and cathepsin (Cat) B/D-positive lysosomes decreases steeply past the proximal segment...
June 15, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29907326/fgf21-protects-human-umbilical-vein-endothelial-cells-against-high-glucose-induced-apoptosis-via-pi3k-akt-fox3a-signaling-pathway
#6
Dongmin Guo, Lele Xiao, Huijun Hu, Mihua Liu, Lu Yang, Xiaolong Lin
AIMS: Diabetic macroangiopathy is the main cause of morbidity and mortality in patients with diabetes. Endothelial cell injury is a pathological precondition for diabetic macroangiopathy. Fibroblast growth factor 21 (FGF21) is a key metabolic regulator which has recently been suggested to protect cardiac myocytes and vascular cells against oxidative stress-induced injury in vitro and vivo. In this study, we aimed to investigate the protective capacity of FGF21 in human umbilical vein endothelial cells (HUVECs) against high glucose (HG)-induced apoptosis via phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt)/FoxO3a pathway...
May 25, 2018: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/29906411/dermal-fibroblast-slc3a2-deficiency-leads-to-premature-aging-and-loss-of-epithelial-homeostasis
#7
Floriane S Tissot, Soline Estrach, Etienne Boulter, Laurence Cailleteau, Lionel Tosello, Laetitia Seguin, Sabrina Pisano, Stéphane Audebert, Olivier Croce, Chloé C Féral
Skin homeostasis relies on fine tuning of epidermis/dermis interactions and is affected by aging. While extracellular matrix (ECM) proteins, such as integrins, are involved in aging, the molecular basis of the skin changes need to be further investigated. Here, we showed that integrin co-receptor, SLC3A2, required for cell proliferation, is expressed at the surface of resting dermal fibroblasts (DF) in young patients, and drastically reduced with aging. In vivo SLC3A2 DF deletion induced major skin phenotypes resembling premature aging...
June 12, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29906228/changes-in-cardiac-resident-fibroblast-physiology-and-phenotype-in-aging
#8
JoAnn Trial, Katarzyna A Cieslik
The cardiac fibroblast plays a central role in tissue homeostasis and in repair after injury. With aging, dysregulated cardiac fibroblasts have a reduced capacity to respond to transforming growth factor-β (TGF-β) and poorly differentiate into contractile myofibroblasts. That results in the formation of an insufficient scar after myocardial infarction (MI). By contrast, in the uninjured aged heart fibroblasts are activated and acquire a pro-fibrotic phenotype that leads to interstitial fibrosis, ventricular stiffness, and diastolic dysfunction, all conditions that may lead to heart failure...
June 15, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29905853/2-methoxyestradiol-inhibits-hypoxia-induced-scleroderma-fibroblast-collagen-synthesis-by-phosphatidylinositol-3-kinase-akt-mtor-signalling
#9
Xing Zhou, Chaofan Liu, Jinghao Lu, Lubing Zhu, Ming Li
Objectives: To investigate the mechanism of 2-methoxyestradiol (2-ME) in inhibiting hypoxia-induced collagen synthesis of fibroblasts in SSc. Methods: The expressions of hypoxia-inducible factor 1 alpha (HIF-1α) and connective tissue growth factor (CTGF) in skin specimens derived from SSc patients and healthy volunteers were examined by immunohistochemistry. HIF-1α was knocked down by lentiviral transduction, and SSc dermal fibroblasts cultured under normoxic (21% O2) or hypoxic (1% O2) condition were treated with PI3K inhibitor LY294002, rapamycin or 2-ME (25 μM)...
June 13, 2018: Rheumatology
https://www.readbyqxmd.com/read/29903916/insulin-like-growth-factor-1-receptor-stabilizes-the-etv6-ntrk3-chimeric-oncoprotein-by-blocking-its-kpc1-rnf123-mediated-proteasomal-degradation
#10
Cristina E Tognon, Bo Rafn, Naniye Malli Cetinbas, Takumi Kamura, Genny Trigo, Barak Rotblat, Fumihiko Okumura, Masaki Matsumoto, Christine Chow, Monika Davare, Michael Pollak, Thibault Mayor, Poul H Sorensen
Many oncogenes, including chimeric oncoproteins, require insulin-like growth factor 1 receptor (IGF1R) for promoting cell transformation. The ETS variant 6 (ETV6)-neurotrophic receptor tyrosine kinase 3 (NTRK3) (EN) chimeric tyrosine kinase is expressed in mesenchymal, epithelial, and hematopoietic cancers and requires the IGF1R axis for transformation. However, current models of IGF1R-mediated EN activation are lacking mechanistic detail. We demonstrate here that IGF-mediated IGF1R stimulation enhances EN tyrosine phosphorylation and that blocking IGF1R activity or decreasing protein levels of the adaptor protein insulin receptor substrate 1/2 (IRS1/2) results in rapid EN degradation...
June 14, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29902550/fgf-binding-proteins-fgfbps-modulators-of-fgf-signaling-in-the-developing-adult-and-stressed-nervous-system
#11
REVIEW
Thomas Taetzsch, Vanessa L Brayman, Gregorio Valdez
Members of the fibroblast growth factor (FGF) family are involved in a variety of cellular processes. In the nervous system, they affect the differentiation and migration of neurons, the formation and maturation of synapses, and the repair of neuronal circuits following insults. Because of the varied yet critical functions of FGF ligands, their availability and activity must be tightly regulated for the nervous system, as well as other tissues, to properly develop and function in adulthood. In this regard, FGF binding proteins (FGFBPs) have emerged as strong candidates for modulating the actions of secreted FGFs in neural and non-neural tissues...
June 11, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29901385/integration-of-a-superparamagnetic-scaffold-and-magnetic-field-to-enhance-the-wound-healing-phenotype-of-fibroblasts
#12
Suisui Hao, Yu Zhang, Jie Meng, Jian Liu, Tao Wen, Ning Gu, Haiyan Xu
Most of the existing scaffolds for guiding tissue regeneration do not provide direct mechanical stimulation to the cells grown on them. In this work, we used nanofibrous superparamagnetic scaffolds with applied magnetic fields to build a "dynamic" scaffold platform and investigated the modulating effects of this platform on the phenotypes of fibroblasts. The results of enzyme-linked immunosorbent and transwell assays indicated that fibroblasts cultivated in this platform secreted significantly higher type I collagen, vascular endothelial growth factor A, and transforming growth factor-β1 and did so in a time-dependent manner...
June 14, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29901190/curcumin-suppresses-cardiac-fibroblasts-activities-by-regulating-the-proliferation-and-cell-cycle-via-the-inhibition-of-the-p38-mapk-erk-signaling-pathway
#13
Guanhua Fang, Shaoqin Chen, Qiuyu Huang, Liangwan Chen, Dongshan Liao
Cardiac fibrosis is a deleterious effect of many cardiovascular diseases. Previous studies have shown that curcumin has exhibited protective effects on cardiovascular diseases. The aim of the present study was to evaluate the effects of curcumin on the activity of human cardiac fibroblasts (CFs) and to elucidate the underlying mechanisms involved. Human CFs were incubated with or without curcumin (20 µmol/l) and transforming growth factor β1 (TGF‑β1; 10 ng/ml), and the expression of α‑smooth muscle actin (α‑SMA), collagen type Iα (COLA)‑1 and COLA3 was evaluated using reverse transcription‑quantitative polymerase chain reaction and western blot analysis...
June 1, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29901171/sipi-soup-inhibits-cancer%C3%A2-associated-fibroblast-activation-and-the-inflammatory-process-by-downregulating-long-non%C3%A2-coding-rna-hipk1%C3%A2-as
#14
Bingxiu Zhou, Yuanyuan Yu, Lixia Yu, Binfu Que, Rui Qiu
Sipi soup (SPS), the aqueous extract derived from the root bark of Sophora japonical L, Salix babylonica L., Morus alba L., as well as Amygdalus davidiana (Carr.) C. de Vos, is a traditional Chinese medicine frequently used to prevent and treat infection and inflammation. However, the role of SPS in cancer‑associated fibroblasts (CAFs) require further investigation. In the present study, the effects of SPS on fibroblast inactivation and the underlying mechanism were investigated. Reverse transcription‑quantitative polymerase chain reaction was used to analyze the mRNA expression levels of fibroblast activation protein (FAP), interleukin (IL)‑6, α‑smooth muscle actin (α‑SMA) and programmed cell death 4 (PDCD4)...
June 6, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29901093/efficacy-of-lentivirus%C3%A2-mediated-drosophila-melanogaster-deoxyribonucleoside-kinase-combined-with-e-%C3%A2-5%C3%A2-2%C3%A2-bromovinyl-%C3%A2-2-%C3%A2-deoxyuridine-or-1%C3%A2-%C3%AE-%C3%A2-d%C3%A2-arabinofuranosylthymine-therapy-in-human-keloid-fibroblasts
#15
Yiqun Sun, Haiyang Jiang, Ming Gu, Xinyu Zheng
Keloid scarring is a type of fibroproliferative disease with a high recurrence rate. However, no effective treatment is currently available. Combined therapy with recombinant lentivirus‑mediated Drosophila melanogaster deoxyribonucleoside kinase (Dm‑dNK) and prodrug has been widely studied and used for cancer treatment. Due to the similarities between keloid scars and tumors, the aim of the present study was to investigate the efficacy of a Dm‑dNK/nucleoside analog system for the treatment of keloid scars...
May 30, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29901090/il%C3%A2-1%C3%AE-and-tnf%C3%A2-%C3%AE-suppress-tgf%C3%A2-%C3%AE-%C3%A2-promoted-ngf-expression-in-periodontal-ligament%C3%A2-derived-fibroblasts-through-inactivation-of-tgf%C3%A2-%C3%AE-%C3%A2-induced-smad2-3%C3%A2-and-p38-mapk%C3%A2-mediated-signals
#16
Maiko Ohta, Naoyuki Chosa, Seiko Kyakumoto, Seiji Yokota, Naoto Okubo, Akira Nemoto, Masaharu Kamo, Shigeharu Joh, Kenichi Satoh, Akira Ishisaki
Mechanosensitive (MS) neurons in the periodontal ligament (PDL) pass information to the trigeminal ganglion when excited by mechanical stimulation of the tooth. During occlusal tooth trauma of PDL tissues, MS neurons are injured, resulting in atrophic neurites and eventual degeneration of MS neurons. Nerve growth factor (NGF), a neurotrophic factor, serves important roles in the regeneration of injured sensory neurons. In the present study, the effect of pro‑inflammatory cytokines, including interleukin 1β (IL‑1β) and tumor necrosis factor α (TNF‑α), on transforming growth factor β1 (TGF‑β1)‑induced NGF expression was evaluated in rat PDL‑derived SCDC2 cells...
June 4, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29899865/oleanolic-acid-induces-p53-dependent-apoptosis-via-the-erk-jnk-akt-pathway-in-cancer-cell-lines-in-prostatic-cancer-xenografts-in-mice
#17
Gyeong-Ji Kim, Hyeon-Ju Jo, Kwon-Jai Lee, Jeong Woo Choi, Jeung Hee An
We evaluated oleanolic acid (OA)-induced anti-cancer activity, apoptotic mechanism, cell cycle status, and MAPK kinase signaling in DU145 (prostate cancer), MCF-7 (breast cancer), U87 (human glioblastoma), normal murine liver cell (BNL CL.2) and human foreskin fibroblast cell lines (Hs 68). The IC50 values for OA-induced cytotoxicity were 112.57 in DU145, 132.29 in MCF-7, and 163.60 in U87 cells, respectively. OA did not exhibit toxicity in BNL CL. 2 and Hs 68 cell lines in our experiments. OA, at 100 µg/mL, increased the number of apoptotic cells to 27...
May 29, 2018: Oncotarget
https://www.readbyqxmd.com/read/29899382/constitutive-ip-3-signaling-underlies-the-sensitivity-of-b-cell-cancers-to-the-bcl-2-ip-3-receptor-disruptor-bird-2
#18
Mart Bittremieux, Rita M La Rovere, Haidar Akl, Claudio Martines, Kirsten Welkenhuyzen, Kathia Dubron, Myriam Baes, Ann Janssens, Peter Vandenberghe, Luca Laurenti, Katja Rietdorf, Giampaolo Morciano, Paolo Pinton, Katsuhiko Mikoshiba, Martin D Bootman, Dimitar G Efremov, Humbert De Smedt, Jan B Parys, Geert Bultynck
Anti-apoptotic Bcl-2 proteins are upregulated in different cancers, including diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL), enabling survival by inhibiting pro-apoptotic Bcl-2-family members and inositol 1,4,5-trisphosphate (IP3 ) receptor (IP3 R)-mediated Ca2+ -signaling. A peptide tool (Bcl-2/IP3 R Disruptor-2; BIRD-2) was developed to abrogate the interaction of Bcl-2 with IP3 Rs by targeting Bcl-2's BH4 domain. BIRD-2 triggers cell death in primary CLL cells and in DLBCL cell lines...
June 13, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29894633/cross-linked-enzyme-aggregates-as-versatile-tool-for-enzyme-delivery-application-to-polymeric-nanoparticles
#19
Marianna Galliani, Melissa Santi, Ambra Del Grosso, Antonella Cecchettini, Filippo M Santorelli, Sandra L Hofmann, Jui-Yun Lu, Lucia Angella, Marco Cecchini, Giovanni Signore
Polymeric nanoparticles (NPs) represent one of the most promising tools in nanomedicine and have been extensively studied for the delivery of water-insoluble drugs. However, the efficient loading of therapeutic enzymes and proteins in polymer-based nanostructures remains an open challenge. Here, we report a synthesis method for a new enzyme delivery system based on cross linked enzyme aggregates (CLEAs) encapsulation into poly(lactide-co-glycolide) (PLGA) NPs. We tested the encapsulation strategy on four enzymes currently investigated for enzyme replacement therapy: palmitoyl protein thioesterase 1 (PPT1; defective in NCL1 disease), galactosylceramidase (GALC; defective in globoid cell leukodystrophy), alpha glucosidase (aGLU; defective in Pompe disease) and beta glucosidase (bGLU; defective in Gaucher's disease)...
June 12, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29893408/crocin-a-natural-molecule-with-potentially-beneficial-effects-against-skin-aging
#20
D Fagot, D M Pham, J Laboureau, E Planel, L Guerin, C Nègre, M Donovan, B A Bernard
OBJECTIVE: Oxidative stress and low grade chronic inflammation stand out as key features of physiological skin aging. The aim of this study was to examine in normal human epidermal keratinocytes (NHEK) and human dermal fibroblasts (HDF) grown in vitro, the antioxidant and anti-inflammatory properties of crocin, a carotenoid glycoside responsible for the color of saffron. Moreover, considering the newly emerging field of skin glycobiology and the presence of two gentiobiosyl moieties in crocin, the effect of crocin on NHEK glycosylation pathways was for the first time investigated...
June 12, 2018: International Journal of Cosmetic Science
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